Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.

There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO2/FiO2 ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 × 103/µl) but had increased in three of these five patients at last follow-up (range 0.23-1.02 × 103/µl). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.

Major thrombocytopenia after balloon-expandable transcatheter aortic valve replacement: prognostic implications and comparison to surgical aortic valve replacement.

OBJECTIVES: We sought to investigate the magnitude and clinical importance of thrombocytopenia post transcatheter aortic valve replacement (TAVR). BACKGROUND: Thrombocytopenia has been observed after TAVR but has not been well studied. METHODS: Major thrombocytopenia (platelet count <100 × 10(9) /L) was studied following aortic valve interventions in a single center. Changes in platelets were compared in 246 patients undergoing balloon-expandable TAVR and a similar population of 57 cases undergoing surgical aortic valve replacement (SAVR in the US PARTNER IA trial). RESULTS: An early drop in platelets was seen on the day of intervention. The drop day 1 post procedure was similar but slightly greater with SAVR vs. TAVR. In both platelet counts continued to drop, reaching a nadir of approximately 50-60% of the baseline platelet count at day 2-3, starting to recover after day 5. Early major thrombocytopenia occurred post TAVR in 37% of patients but was not significantly related to major bleeding (OR 0.89, 95% CI 0.51-1.60, P = 0.69) or risk of stroke (HR 0.61, 95% CI 0.16-2.20, P = 0.45); there was a trend to greater acute kidney injury (OR 1.76, 95% CI 0.95-3.26, P = 0.073) and mortality (HR 1.47, 95% CI 0.98-2.22, P = 0.065). Major thrombocytopenia was persistent in 7.7% of patients and this was independently associated with mortality (HR 3.65, 95% CI 1.63-8.16, P = 0.002). CONCLUSIONS: Post-TAVR thrombocytopenia is a common phenomenon and its magnitude appears similar to that seen after SAVR. It is most often transient, not associated with adverse sequelae and, unless persistent, should be managed in an expectant fashion. © 2014 Wiley Periodicals, Inc.

A prospective, nonrandomized, open-labeled pilot study investigating the use of magnesium in patients undergoing nonacute percutaneous coronary intervention with stent implantation.

BACKGROUND: Magnesium has recently been shown to inhibit acute stent thrombosis in animal models. This study tested the feasibility of magnesium administration in patients undergoing nonacute percutaneous coronary intervention with stent implantation. METHODS: Twenty-one patients undergoing nonemergent percutaneous coronary intervention were enrolled and received intravenous magnesium sulfate (2-g bolus over 20 minutes prepercutaneous coronary intervention, followed by 14 g over 12 hours infusion). ENDPOINTS: safety outcomes--hypotension, bradycardia, bleeding complications and heart block within first 24 hours; angiographic outcomes--acute thrombotic occlusion and need for platelet glycoprotein IIb/IIIa inhibitor bailout; and clinical outcomes--death, myocardial infarction, recurrent ischemia, and need for urgent revascularization at 48 hours and 30 days. RESULTS: No significant effects on heart rate or blood pressure, major bleeding complication, or new electrocardiographic changes were observed. Angiographic thrombus was visualized in two cases, and coronary artery dissection in one case poststent deployment. None of these cases required the use of glycoprotein inhibitors for bailout. Death, myocardial infarction, recurrent ischemia, and need for urgent revascularization were not observed. The serum magnesium level increased from 2.1 +/- 0.3 mg/dL at baseline to 3.5 +/- 0.8 mg/dL at the end of the infusion (P <.0001). Platelet activation was significantly inhibited at the end of the magnesium sulfate infusion. CONCLUSION: Intravenous magnesium sulfate has been demonstrated as a feasible and safe agent in patients undergoing nonacute percutaneous coronary intervention with stent implantation. A randomized clinical trial comparing magnesium with glycoprotein inhibitors during percutaneous coronary intervention is warranted.

Aortic annular sizing for transcatheter aortic valve replacement using cross-sectional 3-dimensional transesophageal echocardiography.

OBJECTIVES: This study compared cross-sectional three-dimensional (3D) transesophageal echocardiography (TEE) to two-dimensional (2D) TEE as methods for predicting aortic regurgitation after transcatheter aortic valve replacement (TAVR). BACKGROUND: Data have shown that TAVR sizing using cross-sectional contrast computed tomography (CT) parameters is superior to 2D-TEE for the prediction of paravalvular aortic regurgitation (AR). Three-dimensional TEE can offer cross-sectional assessment of the aortic annulus but its role for TAVR sizing has been poorly elucidated. METHODS: All patients had severe symptomatic aortic stenosis and were treated with balloon-expandable TAVR in a single center. Patients studied had both 2D-TEE and 3D imaging (contrast CT and/or 3D-TEE) of the aortic annulus at baseline. Receiver-operating characteristic curves were generated for each measurement parameter using post-TAVR paravalvular AR moderate or greater as the state variable. RESULTS: For the 256 patients studied, paravalvular AR moderate or greater occurred in 26 of 256 (10.2%) of patients. Prospectively recorded 2D-TEE measurements had a low discriminatory value (area under the curve = 0.52, 95% confidence interval: 0.40 to 0.63, p = 0.75). Average cross-sectional diameter by CT offered a high degree of discrimination (area under the curve = 0.82, 95% confidence interval: 0.73 to 0.90, p < 0.0001) and mean cross-sectional diameter by 3D-TEE was of intermediate value (area under the curve = 0.68, 95% confidence interval: 0.54 to 0.81, p = 0.036). CONCLUSIONS: Cross-sectional 3D echocardiographic sizing of the aortic annulus dimension offers discrimination of post-TAVR paravalvular AR that is significantly superior to that of 2D-TEE. Cross-sectional data should be sought from 3D-TEE if good CT data are unavailable for TAVR sizing.